USE OF TRIAZINE INHIBITORS IN MAPPING THE ACTIVE-SITE REGION OF LACTOBACILLUS-CASEI DIHYDROFOLATE-REDUCTASE

A quantitative structure-activity relationship for the inhibition of L. casei dihydrofolate reductase (EC 1.5.1.3) by 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3-X-phenyl)-s-triazines was derived as log 1/C = 0.53 .pi.3 - 0.67 log (.beta. .cntdot. 10.pi. + 1) + 0.79MR'' + 3.13 where log .beta. = -3.46 and r = 0.949 for 28 congeners. C is the molar concentration of triazine causing 50% inhibition, .pi.3 is the hydrophobic constant for the 3-X-phenyl substituent. MR'' is the molar refractivity of certain substituents, .beta. is an iteratively derived coefficient and r is the multiple least squares correlation coefficient. This correlation is different from those found with the same type of inhibitors acting on bovine and rat liver dihydrofolate reductase. The differences were discussed. The correlation equations for the triazines acting on purified enzymes were compared with equations correlating triazines inhibiting the growth of Staphylococcus aureus and Escherichia coli.